Endo 6 Flashcards
CRH receptor
Gs-linked receptor [cAMP]
ADH receptor
Gq-linked receptor [IP3/DAG]
ACTH receptor
Gs-linked receptor [cAMP]
Glucocorticoids and androgen receptors
nuclear receptors
CRH/ADH synthesis and release. Inhibitory influences
alpha 1-adrenergic nerves stimulate pre-pro CRH/ADH gene expression and copulsatile release of both releasing hormones
-physiological levels of cortisol inhibit pre-proTRH/ADH gene expression
ACTH synthesis and release
CRH interacts with Gs receptor -incrases cAMP -increases POMC synthesis -increased convertase synthesis ADH interacts with Gq linked receptor -increased IP3/DAG -Ca2+ mobilization -increased ACTH release
Regulation of steroidogenesis
- cholesterol delivery into the mitochondria is the rate-limiting step in steroidogenesis
- as it enters the inner chamber, it is converted to the steroid, pregnenolone, by the action of the enzyme P450 side chain cleavage
- cholesterol channel allows it to move (insertion of StAR protein into membrane) ACTH sitmulates this insertion into the membrane
Adrenocorticosteroidogenesis
- glucocorticoids (controlled by ACTH)
- androgens (controlled by ACTH)
- mineralcorticoids
Deactivation and Excretion
Biotransformation
-potent steroids are converted into steroids that have low biological activity and are more water soluble
Conjugation
-formation of steroid sulphates and steroid glucouronides by liver
Excretion
via urine and some via bile
Modes of action for adrenocorticosteroisd
genomic effects -modification of gene expression Non-genomic effects -mRNA stability -transmembrane currents -Ca2+ levels -phosphorylating events
Physiological roles of adrenal androgens
- produced in males and females
- excess androgen production can cause hirsuitism/masculination in females
Cortisol
- stimulates gluconeogenesis
- cortisol is also released as part of the body’s response to stress
Immunosuppressive actions of glucocorticoids
- inhibits chemo-attraction of immune cells for inflammation sites
- decreases cytokine production
- reduces the production of some immune response cells
Cortisol excess
cushing’s syndrome
-hyperglycaemia, increased lipolysis and protein catabolism, increased adrenal androgens, increased urination
Adrenal cortical insufficiency
addison’s disease
-hypoglycaemia but weight loss due to decreased appetite
-depletion of liver and muscle glycogen
-increased urea, depression, weakness
Waterhouse-Friderichsen Syndrome
-adrenal haemorrhage and insufficiency due to neisseria meningitidis